ALENDRONATE TABLETS

Alendronate belongs to a group of non-hormonal medicines known as bisphosphonates, which prevent bone loss from the body.

Alendronate is used to treat a condition called osteoporosis (brittle bones). This condition is common in women after the menopause. The earlier a woman reaches the menopause, the greater the risk of her developing osteoporosis.

Without treatment, osteoporosis can cause thinning and weakening of the bones in the skeleton which can then lead to fractures, usually of the hip, backbone and wrists. Fractures can occur easily in people suffering from osteoporosis including during normal everyday activities such as heavy lifting or from a minor injury or fall.

Alendronate helps to prevent bone loss and to build up bone which may have been lost due to osteoporosis. It can therefore reduce the risk of back and hip fractures.

What you need to know before you take Alendronate

If you are allergic to Alendronate or any of the other ingredients of this medicine (listed in section 6)

If you have certain disorders of the oesophagus (this is also called the gullet and is the tube that connects your mouth with your stomach) such as narrowing of the gullet or difficulty swallowing

If your doctor has told you that you have low calcium levels in your blood

If you are unable to stand or sit upright for at least 30 minutes at a time.

If you have inflammation of the stomach lining or the duodenum (first section of the small intestine)

If you have a stomach ulcer or other digestive problems including bleeding in the stomach

If you have had surgery on your stomach or gullet in the last year (not including pyloroplasty which is where the outlet from the stomach is widened)

If your doctor has told you that you have Barrett’s oesophagus (a condition associated with changes in the cells that line the lower oesophagus)

If you have or have ever had any kidney problems

If you have or have ever had low vitamin D levels. If so your doctor may wish to monitor your vitamin D levels during treatment with alendronic acid

If you have or have had a condition called hypoparathyroidism (a condition where your parathyroid gland does not work properly)

If you have or have had pain, swelling or numbness of the jaw, loosening of a tooth or a ‘heavy jaw feeling’

If you are undergoing dental treatment or you are to undergo dental surgery

If you have cancer, are undergoing chemotherapy or radiotherapy, are taking steroids, do not receive regular dental care, have a mouth infection or smoke. If so your doctor may want you to have a dental examination before starting the treatment.

It is important to maintain good oral hygiene when being treated with Alendronate 70mg Tablets. You should have routine dental check-ups throughout your treatment and you should contact your doctor or dentist if you experience any problems with your mouth or teeth such as loose teeth, pain or swelling.

Other medicines and Alendronate Tablets

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take any other medicines orally (by mouth) at the same time as taking Alendronate 70mg Tablets. You should leave at least 30 minutes between your dose of Alendronate 70mg Tablets and any other oral medicines. It is important that you follow all of the advice given in section 3 – ‘How to take Alendronic Acid 70mg Tablets.’

You should speak to your doctor before you take Alendronate 70mg Tablets if you are currently taking a non-steroidal anti-inflammatory drug (NSAID).

Pregnancy, breast-feeding and fertility

Do not take Alendronate 70mg Tablets if you are pregnant, think you may be pregnant or are breast-feeding.

Driving and using machines

Alendronate 70mg Tablets are not expected to have any effects on your ability to drive and use machines. However in rare cases patients taking Alendronate 70mg Tablets can suffer from side effects including dizziness, severe muscle, joint and bone pain and eye pain or inflammation. If you are affected in this way, you should contact your doctor before driving or using machinery.

How to take Alendronate

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Alendronate 70mg Tablets must be taken once a week.

Adults:

The following instructions are particularly important to ensure that your medicine is effective and to reduce the likelihood of the medicine irritating your oesophagus (gullet):

Choose the day of the week that best suits you to take your tablet.

Take one Alendronate 70mg Tablet each week on your chosen day.

Immediately after getting up on your chosen day, take the Alendronate 70mg Tablet on an empty stomach. It should only be taken with a full glass of plain water (not less than 200ml) and should be taken at least 30 minutes before any other food, drink or medicine. Do not take your tablet with tea, coffee, mineral water or juice.

The tablet must be swallowed whole.You must not chew or crush the tablet or allow it to dissolve in your mouth.

Wait at least 30 minutes after taking the tablet before you drink or eat the first meal of the day or take any other medicine (this includes calcium supplements, vitamins and antacids (which are used to treat indigestion)).

Do not lie down after taking Alendronate 70mg Tablets. You must stay upright (sitting, standing or walking) for at least 30 minutes after you have swallowed the tablet. It is also important that you do not lie down before you have eaten the first meal of the day.

Do not take your tablet at bedtime or before you get out of bed in the morning.

If you find it difficult and/or painful to swallow, or you feel pain behind the breast-bone or new or worsened heartburn, stop taking the tablets and contact your doctor.

Your doctor may also ask you to take vitamin D or calcium supplements whilst you are taking Alendronate 70mg Tablets. If so, you should follow your doctor’s advice carefully.

It is important that you continue to take Alendronate 70mg Tablets for as long as your doctor recommends. Alendronate 70mg Tablets can only treat your osteoporosis effectively if you continue to take the tablets.

Children:

Alendronate 70mg Tablets should not be given to children and adolescents.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

All medicines can cause allergic reactions, although serious allergic reactions are very rare. You should stop taking Alendronate 70mg Tablets and tell your doctor immediately if you get any of the following symptoms:

sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body). This is known as ‘angioedema’.

a rash, blistering or other effects on the skin, eyes, mouth or genitals, itching or high temperature (symptoms of severe skin reactions called Stevens-Johnson syndrome or toxic epidermal necrolysis).

If you have difficulty and/or pain when swallowing, you feel pain behind the breast-bone or new or worsened heartburn, stop taking Alendronate 70mg Tablets and contact your doctor.

If you ignore these symptoms and continue to take your tablets it is likely that these gullet reactions may get worse.

The following side effects have been reported:

Very common side effects (probably affecting more than 1 in 10 people)

Treatment of osteoporosis in men at increased risk of fracture. A reduction in the incidence of vertebral, but not of non-vertebral fractures has been demonstrated.

Prophylaxis of glucocorticoid-induced osteoporosis.

Risk factors often associated with the development of osteoporosis include thin body build, family history of osteoporosis, early menopause, moderately low bone mass and long-term glucocorticoid therapy, especially with high doses (15 mg/day).

Method of administration

Posology

The optimal duration of bisphosphonate treatment for osteoporosis has not been established. The need for continued treatment should be re-evaluated periodically based on the benefits and potential risks of Alendronic Acid 10 mg Tablets on an individual patient basis, particularly after 5 or more years of use.

Treatment of post-menopausal osteoporosis:

The recommended dosage is 10 mg once daily.

Treatment of osteoporosis in men:

The recommended dosage is 10 mg once daily.

Treatment and Prevention of glucocorticoid-induced osteoporosis:

For post-menopausal women who are not receiving oestrogen treatment the recommended dose is one 10 mg tablet daily. For other populations, see summary of product characteristics for preparations that contain 5 mg alendronate

Elderly In clinical trials there was no age-related difference with regard to efficacy or safety profiles of alendronate. Therefore no adjustment of the dose is necessary for elderly patients.

Renal impairment

No dose adjustment is necessary in patients with a glomerular filtration rate (GFR) greater than 35 ml/min. Alendronate is not recommended for patients with impaired renal function if the GFR is less than 35 ml/min, as there is no experience of this.

Use in impaired hepatic function No dose adjustment is necessary.

Paediatric population Alendronate Sodium is not recommended for use in children under the age of 18 years due to insufficient data on safety and efficacy in conditions associated with paediatric osteoporosis (See also section 5.1).

Method of administration

Oral use.

To obtain satisfactory absorption of alendronate Alendronic acid tablets must be taken on an empty stomach immediately on rising in the morning, with plain water only, at least 30 minutes before the first food, drink or other medication of the day. Other drinks (including mineral water), food and some medicines are likely to reduce the absorption of alendronate (see section 4.5).

To assist delivery to the stomach and thus reduce the risk of irritation/side effects locally and in the oesophagus (see section 4.4)

Alendronic acid tablets should only be swallowed on rising for the day with a whole glass of water (not less than 200 ml).

Alendronic acid tablets should be swallowed whole. The tablets should not be chewed, sucked or allowed to dissolve in the mouth on account of the risk of oropharyngeal ulceration.

Patients should not lie down until after the first meal of the day, which must be at least 30 minutes after taking the tablet.

Patients should not lie down within 30 minutes of taking Alendronic acid tablets

Alendronic acid tablets should not be taken at bedtime or before arising for the day.

Patients should be given a calcium and vitamin D supplement if the diet is inadequate (see section 4.4).

Contraindications

Alendronic acid Tablet is contraindicated in:

Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achalasia.

Inability to stand or sit upright for at least 30 minutes.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Hypocalcaemia.

Special warnings and precautions for use

Upper gastrointestinal adverse reactions

Alendronic acid can cause local irritation of the upper gastro-intestinal mucosa. Because there is a potential for worsening of the underlying disease, caution should be used when alendronic acid is given to patients with active upper gastro-intestinal problems, such as dysphagia, oesophageal disease, gastritis, duodenitis, or ulcers or with a recent history (within the previous year) of major gastro-intestinal disease such as peptic ulcer, or active gastro-intestinal bleeding, or surgery of the upper gastro-intestinal tract other than pyloroplasty (see section 4.3). In patients with known Barrett’s oesophagus, prescribers should consider the benefits and potential risks of alendronate on an individual patient basis.

Oesophageal reactions (sometimes severe and requiring hospitalisation), such as oesophagitis, oesophageal ulcers and oesophageal erosions, rarely followed by oesophageal stricture or perforation, have been reported in patients receiving alendronic acid. Physicians should therefore be alert to any signs or symptoms signalling a possible oesophageal reaction and patients should be instructed to discontinue alendronic acid and seek medical attention if they develop symptoms of oesophageal irritation such as dysphagia, pain on swallowing or retrosternal pain, new or worsening heartburn.

The risk of severe oesophageal adverse experiences appears to be greater in patients who fail to take alendronic acid tablet properly and/or who continue to take alendronic acid tablet after developing symptoms suggestive of oesophageal irritation. It is very important that the full dosing instructions are provided to, and understood by the patient (see section 4.2). Patients should be informed that failure to follow these instructions may increase their risk of oesophageal problems.

While no increased risk was observed in extensive clinical trials, there have been rare (post-marketing) reports of gastric and duodenal ulcers, some severe and with complications.

Osteonecrosis of the jaw

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection (including osteomyelitis) has been reported in patients with cancer receiving treatment regimens including primarily intravenously administered bisphosphonates. Many of these patients were also receiving chemotherapy and corticosteroids. Osteonecrosis of the jaw has also been reported in patients with osteoporosis receiving oral bisphosphonates.

The following risk factors should be considered when evaluating an individual’s risk of developing osteonecrosis of the jaw:

potency of the bisphosphonate (highest for zoledronic acid), route of administration (see above) and cumulative dose

A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with poor dental status.

While on treatment, these patients should avoid invasive dental procedures if possible. For patients who develop osteonecrosis of the jaw while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw.

Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

During bisphosphonate treatment, all patients should be encouraged to maintain good oral hygiene, receive routine dental check-ups, and report any oral symptoms such as dental mobility, pain or swelling.

Osteonecrosis of the external auditory canal

Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections.

Musculoskeletal pain

Bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. In post-marketing experience, these symptoms have rarely been severe and/or incapacitating (see section 4.8). The time to onset of symptoms varied from one day to several months after starting treatment. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.

Atypical fractures of the femur

Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment.

During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture.

Skin reactions

In post-marketing experience, there have been rare reports of severe skin reactions including Stevens Johnson syndrome and toxic epidermal necrolysis.

Renal impairment

Alendronic acid Tablet is not recommended for patients with renal impairment where GFR is less than 35 ml/min, (see section 4.2).

Bone and mineral metabolism

Causes of osteoporosis other than oestrogen deficiency, ageing and glucocorticoid use should be considered.

Hypocalcaemia must be corrected before initiating therapy with alendronic acid (see section 4.3). Other disorders affecting mineral metabolism (such as vitamin D deficiency and hypoparathyroidism) should also be effectively treated. In patients with these conditions, serum calcium and symptoms of hypocalcaemia should be monitored during therapy with alendronic acid.

Due to the positive effects of alendronic acid in increasing bone mineral, decreases in serum calcium and phosphate may occur, especially in patients taking glucocorticoids, in whom calcium absorption may be decreased. These are usually small and asymptomatic. However, there have been rare reports of symptomatic hypocalcaemia, which have occasionally been severe and often occurred in patients with predisposing conditions (e.g. hypoparathyroidism, vitamin D deficiency and calcium malabsorption).

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Possible side effects

Immune system disorders:

Rare: hypersensitivity reactions including urticaria and angioedema

Metabolism and nutrition disorders:

Rare: symptomatic hypocalcaemia, often in association with predisposing conditions.